title: Ribose Supplementation Alone or with Elevated Creatine Does Not Preserve High Energy Nucleotides or Cardiac Function in the Failing Mouse Heart.
abstract: Reduced levels of creatine and total adenine nucleotides (sum of ATP, ADP and AMP) are hallmarks of chronic heart failure and restoring these pools is predicted to be beneficial by maintaining the diseased heart in a more favourable energy state. Ribose supplementation is thought to support both salvage and re-synthesis of adenine nucleotides by bypassing the rate-limiting step. We therefore tested whether ribose would be beneficial in chronic heart failure in control mice and in mice with elevated myocardial creatine due to overexpression of the creatine transporter (CrT-OE).
  
  
  
  FOUR GROUPS WERE STUDIED: sham; myocardial infarction (MI); MI+ribose; MI+CrT-OE+ribose. In a pilot study, ribose given in drinking water was bioavailable, resulting in a two-fold increase in myocardial ribose-5-phosphate levels. However, 8 weeks post-surgery, total adenine nucleotide (TAN) pool was decreased to a similar amount (8-14%) in all infarcted groups irrespective of the treatment received. All infarcted groups also presented with a similar and substantial degree of left ventricular (LV) dysfunction (3-fold reduction in ejection fraction) and LV hypertrophy (32-47% increased mass). Ejection fraction closely correlated with infarct size independently of treatment (r(2) = 0.63, p<0.0001), but did not correlate with myocardial creatine or TAN levels.
  
  
  
  Elevating myocardial ribose and creatine levels failed to maintain TAN pool or improve post-infarction LV remodeling and function. This suggests that ribose is not rate-limiting for purine nucleotide biosynthesis in the chronically failing mouse heart and that alternative strategies to preserve TAN pool should be investigated.
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, British Heart Foundation Centre of Research Excellence and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Kiterie M E
authors.initials: KM
authors.lastname: Faller
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Medway
authors.forename: Dunja
authors.initials: D
authors.lastname: Aksentijevic
authors.forename: Liam
authors.initials: L
authors.lastname: Sebag-Montefiore
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Schneider
authors.forename: Craig A
authors.initials: CA
authors.lastname: Lygate
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D003404:Creatinine / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006334:Heart Function Tests; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D010865:Pilot Projects; D012266:Ribose / Q000008:administration & dosage*
chemical_list: D000227:Adenine Nucleotides; D012266:Ribose; D003404:Creatinine